It exposed me, probably in the earliest way, to “Hey, I could do that.” I’ve never been one to love the camera or even to be as drawn to it as I am to the human aspect of it, and I think it was a film that speaks in a very simple way of here’s a way that you can tell a story on film in human terms. It was the kind of film that made me go, “I could do this; I want to tell stories that are like this and told in this way.” And so it was altering for me in that way, in its simplicity or deceptive simplicity.[7]

His play Bash: Latter-Day Plays is a set of three short plays (Iphigenia in orem, A gaggle of saints, and Medea redux) depicting essentially good Latter-day Saints doing disturbing and violent things. It ran Off-Broadway at the Douglas Fairbanks Theatre in 1999. One of the plays, Medea redux, is a one-person performance by Calista Flockhart.[5][8][9] This play resulted in his being disfellowshipped from the LDS Church (i.e., losing some privileges of church membership without being excommunicated). He has since formally left the LDS Church.[10]

In 2001, LaBute wrote and directed the play The Shape of Things, which premièred in London and starred Paul Rudd and Rachel Weisz. It was turned into a film in 2003 with the same cast and director. Set in a small university town in the American Midwest, it focuses on four young students who become emotionally and romantically involved with each other, questioning the nature of art and the lengths to which people will go for love. In the play and film, Weisz's character manipulates Rudd's character into changing everything about himself and discarding his friends in order to become more attractive to her. She even pretends to fall in love with him, prompting an offer of marriage, whereupon she cruelly exposes and humiliates him before an audience, announcing that he has simply been an "art project" for her MFA thesis.

LaBute's 2002 play The Mercy Seat was a theatrical response to the September 11, 2001 attacks.[11][12] Set on September 12, it concerns a man who worked at the World Trade Center but was away from the office during the attack – with his mistress. Expecting that his family believes that he was killed in the towers' collapse, he contemplates using the tragedy to run away and start a new life with his lover. Starring Liev Schreiber and Sigourney Weaver, the play was a commercial and critical success.[citation needed] While hesitant to term The Mercy Seat "political theater", Labute said, "I refer to this play in the printed introduction as a kind of emotional terrorism that we wage on those we profess to love." He dedicated this edition to David Hare, in response to Hare's "straightforward, thoughtful, probing work".[13]

Critics have responded to his plays as having a misanthropic tone.[16][17][18] Rob Weinert-Kendt in The Village Voice referred to LaBute as "American theater's reigning misanthrope".[19]The New York Times said that critics labeled him a misanthrope, on the release of his film, Your Friends & Neighbors. The UK's Independent newspaper dubbed him "America's misanthrope par excellence".[20] Citing In the Company of Men and The Shape of Things, critic Daniel Kimmel identified a thread running through his work: "Neil LaBute is a misanthrope who assumes that only callous and evil people who use and abuse others can survive in this world." Critics labeled him a misogynist after the release of In the Company of Men.[21]

LaBute directed Death at a Funeral, a remake of a 2007 British film of the same name. It was written by Dean Craig (who also wrote the original screenplay) and starred Chris Rock.

LaBute wrote a new Introduction and new scenes for the Chicago Shakespeare Theater production of The Taming of the Shrew by William Shakespeare from April 7 to June 6, 2010. LaBute framed the classic play in overtly metatheatrical terms and added a lesbian romance in a subplot.

LaBute's first produced play, Filthy Talk for Troubled Times (1989) — a series of biting exchanges between two "everyman" characters in a bar – was staged from June 3–5, 2010 by MCC Theater as a benefit for MCC's Playwrights' Coalition and their commitment to developing new work. LaBute also directed the reading. Originally when it premiered in New York City at the Westside Dance Project, the entire audience stood up and booed afterward. One audience member cried out, "Kill The Playwright!"[citation needed]

The Break of Noon premiered Off-Broadway at the Lucille Lortel Theatre in an MCC Theatre production on October 28, 2010 (previews), running to December 22, 2010.[22] The play then opened in Los Angeles at the Geffen Theater, again directed by Bonney, from January 25, opening on February 2 to March 6, 2011. The show stars Tracee Chimo, David Duchovny, John Earl Jelks, and Amanda Peet. The show was directed by Jo Bonney, set design by Neil Patel, costume design by ESosa, lighting design by David Weiner, original music by Justin Ellington and sound design by Darron L.West.[23]

The Unimaginable, a new short play by LaBute, premiered as part of the Terror 2010 season at the Southwark Playhouse in London, UK from October 12 – 31, 2010.

LaBute's style is very language-oriented. His work is terse, rhythmic, and highly colloquial. His style bears similarity to one of his favorite playwrights, David Mamet. LaBute even shares some similar themes with Mamet including gender relations, political correctness, and masculinity.[28]